Αρχειοθήκη ιστολογίου

Τετάρτη 4 Αυγούστου 2021

Lactobacillus acidophilus and vitamin C attenuate ethanol-induced intestinal and liver injury in mice

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Exp Ther Med. 2021 Sep;22(3):1005. doi: 10.3892/etm.2021.10438. Epub 2021 Jul 15.

ABSTRACT

Ethanol exposure frequently induces intestinal and liver injury, dysbiosis of the gut microbiota and vitamin C (VC) deficiency. Gut microbiota-targeted therapy is emerging as an important adjuvant method for protecting the body against ethanol-induced injury, particularly probiotics containing Lactobacillus acidophilus (LA). However, the feasibility and efficiency of using synbiotics containing LA and VC against ethanol-induced injury remained largely undetermined. To examine the advantages of LA+VC, their effect was evaluated in an ethanol-fed mouse model. The results suggested that LA+VC restored gut microbiota homeostasis and reinstated the immune balance of colonic T-regulatory cells (CD4+CD45+forkhead box p3+). In addition, intestinal barrier disorders were improved via upregulating tight junction prot eins (claudin-2, zona occludens-1 and occludin) and mucus secretion, which prevented the translocation of lipopolysaccharide into circulatory systems and subsequently reduced the expression of Toll-like receptor 4 in liver tissues. In this context, LA+VC treatment reduced the inflammatory response in the liver, which was likely responsible for the improved liver function in ethanol-challenged mice. Collectively, these results indicated that LA+VC treatment significantly protected the intestine and liver from ethanol damage by enhancing intestinal barrier function and reducing systemic inflammation. The present study paved the way for further exploration of synbiotics based on Lactobacillus species and VC.

PMID:34345287 | PMC:PMC8311231 | DOI:10.3892/etm.2021.10438

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High serum level of interleukin-6 is linked with dyslipidemia in oral lichen planus

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Exp Ther Med. 2021 Sep;22(3):987. doi: 10.3892/etm.2021.10419. Epub 2021 Jul 13.

ABSTRACT

Oral lichen planus (OLP) is a complex chronic inflammatory disorder in which autocytotoxic CD8+ T cells, locally present in the affected tissue, induce basal keratinocyte apoptosis, through the release of several cytokines, such as interleukin-6 (IL-6). IL-6 is a proinflammatory cytokine that is related to alterations in lipid metabolism in psoriasis patients. Impaired lipid metabolism together with high serum levels of triglycerides have been found in association with OLP. However, the correlation between serum levels of IL-6 and dyslipidemia has not yet been studied in this disorder. The present study aimed to demonstrate the association between OLP, systemic inflammation through increased release of inflammation mediators such as IL-6 and alteration of lipid metabolism, in order to support the concept of OLP as a marker of systemic i nflammation and a potential risk factor of cardiovascular morbidities. For this purpose, we designed a case-control study using a cohort of 18 patients with different clinical forms of OLP compared with 18 control group patients with other oral conditions, to identify a potential correlation between serum levels of IL-6 and serum lipid levels. High plasma serum levels of IL-6 were found to be correlated with cholesterol, high density lipoprotein cholesterol and triglyceride serum levels in the patients with OLP. There was a significant association between erosive and atrophic clinical forms of OLP and the pathological serum values of IL-6 and triglycerides, respectively, making these two parameters good predictive factors of the clinical form of OLP. Further studies of other biomarkers of systemic inflammation using larger cohorts of OLP patients are necessary in order to consider LP as a marker of systemic inflammation and to support the screening of these patients for lipid metabo lism changes and treatment with specific antagonists in order to prevent cardiovascular events.

PMID:34345269 | PMC:PMC8311226 | DOI:10.3892/etm.2021.10419

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Overexpression of HOXD8 inhibits the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression

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Exp Ther Med. 2021 Sep;22(3):1006. doi: 10.3892/etm.2021.10439. Epub 2021 Jul 15.

ABSTRACT

Breast cancer is one of the most common malignant tumors in women. Although a number of homeobox (HOX) genes are known to serve an important role in breast cancer, the role of HOXD8 in breast cancer remains unclear. The aim of the present study was to investigate the role of HOXD8 in the physiological behaviors of breast cancer cells. The Gene Expression Profiling Interactive Analysis database was used to analyze the expression of HOXD8 in patients with breast cancer and in healthy subjects. Western blotting was performed to determine the expression levels of HOXD8 in several breast cancer cell lines; subsequently, HOXD8 expression was knocked down and overexpressed in MCF-7 cells. Cell Counting Kit-8, colony formation, wound healing and Transwell assays were used to evaluate the effects of HOXD8 on breast cancer cell viability, proliferation, mi gration and invasion, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to identify the binding sites between HOXD8 and inhibitor of apoptosis-like protein-2 (ILP2). In addition, ILP2 expression levels were knocked down in MCF-7 cells. The results demonstrated that the expression levels of HOXD8 were significantly downregulated in breast cancer tissues and cell lines, and that the overexpression of HOXD8 inhibited the proliferation, invasion and migration of cancer cells. HOXD8 was shown to bind to the ILP2 promoter to regulate the expression of ILP2. Furthermore, ILP2 knockdown reversed the effects of HOXD8 knockdown on breast cancer cell proliferation, invasion and migration. In conclusion, the findings of the present study suggested that HOXD8 may inhibit the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression.

PMID:34345288 | PMC:PMC8311240 | DOI:10.3892/etm.2021.10439

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Obeticholic acid ameliorates obesity and hepatic steatosis by activating brown fat

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Exp Ther Med. 2021 Sep;22(3):991. doi: 10.3892/etm.2021.10423. Epub 2021 Jul 14.

ABSTRACT

Obeticholic acid (OCA) is exemplified as a potent drug for treating primary biliary cirrhosis and nonalcoholic fatty liver disease by inhibiting bile acid synthesis. However, it remains unclear whether the effect of OCA is mediated by the function of brown adipose tissue (BAT). In the present study, brown adipogenesis differentiation in vitro and db/db mouse model treated with OCA were used to assess the anti-obesity function by body weight tracking, O2 consumption, food intake, physical activity, glucose tolerance tests. In addition, uncoupling protein 1 (Ucp1) protein expression in brown adipose tissue was measured by western blotting, morphometry of brown adipose tissue was analyzed by hematoxylin and eosin staining. Hepatic steatosis was detected by Oil-Red O staining and serological analysis was performed to assess the effec t of OCA on hyperlipidemia. OCA treatment enhanced brown adipocyte cell differentiation and upregulated the expression of the BAT-specific gene Ucp1) in C3H10T1/2 cells in vitro. Consistent with these findings, OCA increased whole-body energy metabolism and glucose homeostasis by enhancing BAT activity in vivo, and ultimately decreased body weight gain in db/db mice. In addition, the results demonstrated that spontaneous hepatic steatosis in db/db mice was ameliorated following OCA treatment. In summary, OCA functioned as a BAT activator to help ameliorate obesity and maintain glucose homeostasis in db/db mice. The present results may provide a novel potential therapeutic approach to activate brown fat in patients with obesity and other metabolic disorders.

PMID:34345273 | PMC:PMC8311225 | DOI:10.3892/etm.2021.10423

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PERFORMANCE OF HANDHELD NAI(TL) SPECTROMETERS AS DOSIMETERS BY LABORATORY AND FIELD DOSE RATE MEASUREMENTS

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Radiat Prot Dosimetry. 2021 Aug 2;194(4):233-248. doi: 10.1093/rpd/ncab098.

ABSTRACT

In the framework of the IAEA Coordinated Research Project (CRP) J02012 on 'Advancing Radiation Detection Equipment for Detecting Nuclear and Other Radioactive Material Out of Regulatory Control', the properties of two commercial instruments (1) InSpector 1000 analyzer (Canberra), with a 2″ × 2″ NaI(Tl) scintillator and (2) RIIDEYE M-G3 analyzer (Thermo Scientific), with a 3″ × 3″ NaI(Tl) s cintillator, were evaluated as dosimeters by laboratory and field measurements. In the Ionizing Radiation Calibration Laboratory (IRCL) of the Greek Atomic Energy Commission, the NaI(Tl) spectrometers were tested in order to measure Ambient gamma Dose Equivalent Rate (ADER). The NaI(Tl) scintillators were irradiated in a homogeneous field with 662 keV photons with different ADER values from 0.17 to 100 μSv h-1 at 0° incidence (irradiation field perpendicular to the detector's front window) and at 90° incidence. For each irradiation, the measured ADER by the spectrometers and the 'true' ADER values (provided by the IRCL) were compared. In addition, the angular dependence (0-359°) of the ADER response of the spectrometers was studied with a 152Eu source placed at 1, 2 and 3 m from the spectrometers. The ADER dependence as function of the distance from the 152Eu source (at 0° incidence) measured by the two detectors was compared with the theoretical one. In the field studies, ADER was measured by the spectrometers at seven locations belonging to the Greek Early Warning System Network (which is based on Reuter-Stokes ionization chambers). These locations have different ADER values ranging from 20 to 120 nSv h-1. In these locations, gamma ADER were also deduced (1) by in situ gamma spectrometry measurements with portable Germanium HPGe detectors and (2) by the Reuter-Stokes ionization chambers (by subtraction of the cosmic radiation). Gamma dose measurements were also performed with the InSpector 1000 and RIIDEYE M-G3 detectors in 25 locations (beaches) of Northern Greece and compared with the ADER values deduced by sand sample analysis with gamma spectroscopy. Beaches with sand are good candidates for such type of measurements since they are commonly flat and in principle the natural radionuclides are homogenously distributed.

PMID:34260730 | DOI:10.1093/rpd/ncab098

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Knockdown of circ_0001883 may inhibit epithelial-mesenchymal transition in laryngeal squamous cell carcinoma via the miR-125-5p/PI3K/AKT axis

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Exp Ther Med. 2021 Sep;22(3):1007. doi: 10.3892/etm.2021.10440. Epub 2021 Jul 15.

ABSTRACT

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with increasing incidence and poor prognosis. Circular RNAs (circRNAs) are known to modulate tumorigenesis and cancer development that may function through microRNAs (miRs). The aim of the present study was to investigate the functional roles of circ_0001883 in LSCC and the underlying molecular mechanism. The expression of circ_0001883 was upregulated and measured using reverse transcription-quantitative PCR (RT-qPCR) and RNase R. miR-125b-5p expression was downregulated in LSCC tissues and cells as determined using RT-qPCR. Subsequently, knockdown of circ_0001883 inhibited LSCC cell migration, invasion and epithelial-mesenchymal transition (EMT), which were tested by wound healing assays, Transwell assays and western blotting, respectively. Bioinformatics analysis predicted that circ_ 0001883 was a sponge of miR-125b-5p, which was verified using a dual-luciferase reporter assay. Knockdown of circ_0001883 played a functional role by sponging miR-125b-5p. Additionally, circ_0001883 and miR-125b-5p influenced phosphorylation of PI3K and AKT, detected via western blotting. In an in vivo study, knockdown of circ_0001883 reduced tumor volume and weight in mice, along with enhanced miR-125b-5p and E-cadherin expression levels, and decreased N-cadherin, phosphorylated (p)-PI3K/PI3K and p-AKT/AKT ratios. In conclusion, knockdown of circ_0001883 inhibited cell migration, invasion and EMT of LSCC by sponging miR-125b-5p. This is hypothesized to be via the PI3K/AKT signaling pathway, which suggested that circ_0001883 has potential for LSCC therapy.

PMID:34345289 | PMC:PMC8311254 | DOI:10.3892/etm.2021.10440

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Orthopedic surgery in hemophilic patients with musculoskeletal disorders: A systematic review

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Exp Ther Med. 2021 Sep;22(3):995. doi: 10.3892/etm.2021.10427. Epub 2021 Jul 14.

ABSTRACT

Hemophilia is a hereditary coagulopathy caused by factor VIII (hemophilia type A) or by coagulation factor IX (hemophilia type B) dysfunction, characterized by an increased bleeding predisposition, which is either spontaneous or secondary to minimal trauma. Currently, hemophilia may also be considered an 'orthopedic' condition, due to the fact that it affects the musculoskeletal system of most hemophilic patients. In recent years, constant prophylaxis using coagulation factors has led to a significant improvement in the hemophilic patient's quality of life, by reducing both life-threatening hemorrhagic phenomena, as well as the occurrence of chronic complications. Nevertheless, progressive joint bleeding remains unavoidable in this category of patients, and the onset of chronic arthropathy with secondary motor deficiency remains the main complicat ion with an invalidating character. In such cases, orthopedic management is imperative; osteoarticular complications being managed most often with the help of conservative or surgical techniques. The purpose of this review is to provide an overview of modern orthopedic practices which are useful in the management of hemophilic patients suffering from osteoarticular disorders.

PMID:34345277 | PMC:PMC8311230 | DOI:10.3892/etm.2021.10427

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DL-3-n-butylphthalide protects H9c2 cardiomyoblasts from ischemia/reperfusion injury by regulating HSP70 expression via PI3K/AKT pathway activation

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Exp Ther Med. 2021 Sep;22(3):1008. doi: 10.3892/etm.2021.10441. Epub 2021 Jul 15.

ABSTRACT

DL-3-n-butylphthalide (NBP) is commonly used to treat ischemic strokes due to its antioxidative and anti-inflammatory effects. The present study aimed to examine the protective effects of NBP on myocardial ischemia-reperfusion injury (MIRI) by establishing a MIRI model in H9c2 cells. Cell viability assay using Cell Counting Kit-8, lactate dehydrogenase (LDH) cytotoxicity and lipid peroxidation malondialdehyde (MDA) content were assessed to detect cell activity, degree of cell injury and oxidative stress reaction. Reverse transcription-quantitative PCR was used to quantify the expression of inflammatory factors in H9c2 cells. Western blotting and immunofluorescence staining were used to detect the protein expression of PI3K/AKT and heat shock protein 70 (HSP70). The present results indicated that NBP significantly increased cell viability during i schemia-reperfusion. Moreover, NBP inhibited the release of LDH and the production of MDA. NBP treatment also significantly decreased the expression of inflammatory factors at the mRNA level. Additionally, NBP activated the PI3K/AKT pathway and upregulated the expression of HSP70 compared with cells in the MIRI model. LY294002, a PI3K inhibitor, reversed the protective effects of NBP and suppressed the expression of HSP70. The present study demonstrated that NBP protected H9c2 cells from MIRI by regulating HSP70 expression via PI3K/AKT pathway activation.

PMID:34345290 | PMC:PMC8311253 | DOI:10.3892/etm.2021.10441

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Optimization of a GF-AAS method for lead testing in blood and urine: A useful tool in acute abdominal pain management in emergency

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Exp Ther Med. 2021 Sep;22(3):985. doi: 10.3892/etm.2021.10417. Epub 2021 Jul 13.

ABSTRACT

Suspicion of lead poisoning is confirmed by its concentration in blood and protoporphyrin red blood cells. At low concentrations, lead influences the synthesis of the heme in the sense of lowering it. Acute and chronic lead intoxication is extremely polymorphic in regards to its clinical manifestations, with digestive, hematological, cardiovascular, renal hepatic and neurological features. The aim of the study was to evaluate the presence of lead in human whole blood and urine harvested before and during chelation treatment in the case of lead poisoning. An atomic absorption spectroscopic method for the analysis of lead was developed using graphite furnace atomic absorption spectrophotometer (GF-AAS), Varian Spectra AA-880 with a hollow cathode lead lamp and a deuterium lamp for background correction, coupled to a GTA-100 atomizer and a programmab le sample dispenser. Standard calibration solutions were used for the range 10-100 µg/l. The linearity range was 10.0 to 100.0 µg/l with the correlation coefficient of 0.999. We established that the method can be applied for the determination of lead in whole blood and urine, and the results obtained are useful for monitoring chelation therapy in cases of acute lead poisoning, a neglected cause of abdominal colic pain in an emergency situation.

PMID:34345267 | PMC:PMC8311247 | DOI:10.3892/etm.2021.10417

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Advances in molecular mechanisms of pelvic organ prolapse (Review)

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Exp Ther Med. 2021 Sep;22(3):1009. doi: 10.3892/etm.2021.10442. Epub 2021 Jul 15.

ABSTRACT

Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directl y caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed.

PMID:34345291 | PMC:PMC8311251 | DOI:10.3892/etm.2021.10442

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